Stress responses and family history effects on depression risk in teen girls

Tracking the Dynamic Trajectory of Behavioral, Physiological, and Neurobiological Stress Responses in Female Adolescents at High and Low Familial Risk for Depression

This project will use brain scans, a smartwatch, and phone surveys to see if stress-related brain and daily-life responses predict future depression in 13–15-year-old girls, especially those with a parent who had depression.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 148 (estimated)
• Ages: 13 Years to 15 Years
• Sex: Female
• Sponsor: Mclean Hospital (Academic / other)
• Locations: 1 site (Belmont, Massachusetts)
• Trial ID: NCT06816329 on ClinicalTrials.gov

What this trial studies

About 148 girls aged 13–15, with and without a biological parent who has had major depressive disorder, will be enrolled and followed across multiple visits spanning 18 months. Participants will complete diagnostic interviews and questionnaires, undergo an fMRI scan at McLean Hospital, and take part in two-week periods of intensive phone surveys (ecological momentary assessment) while wearing a smartwatch that records heart rate, activity, and sleep. The study will link stress-related brain network measures from fMRI with real-world physiological and self-report data to identify patterns associated with short-term changes in mood and coping. Researchers will compare adolescents at high familial risk to those without a parental history to see which brain and behavioral signatures predict later depression onset.

Who should consider this trial

Good fit: Girls aged 13–15 assigned female at birth who are right-handed, fluent in English, have a personal cell phone, can consent/assent, and are willing to complete interviews, wear a smartwatch, and attend an fMRI visit — including those whose biological parent has had MDD.

Not a fit: Individuals who are not assigned female at birth, outside the 13–15 age range, unable to use a smartphone, or who have contraindications to MRI (e.g., implanted metal devices) would not be eligible and therefore would not directly benefit from participation.

Why it matters

Potential benefit: If successful, the work could help identify teens at highest short-term risk so clinicians can target prevention or early treatment before depression develops.

How similar studies have performed: Prior research has linked parental history and altered stress responses to depression risk, but combining task-based fMRI with intensive real-world wearable and phone-based tracking in adolescent girls is relatively novel.

Eligibility criteria

Inclusion Criteria: General Inclusion Criteria for all Adolescent Cohorts:

* Female sex assigned at birth
* Ages 13-15
* English as first language or English Fluency
* Right-handed
* Have a personal cell phone to complete the ecological momentary assessments
* Ability to give signed, informed consent/assent either written or electronic (via RedCap eConsent)
* Normal or corrected to normal vision and hearing

Additional Inclusion Criteria for Female Adolescents with a Parental History of MDD, high-risk group:

• A biological parent meeting DSM-5 criteria for at least one past/current major depressive episode

Exclusion Criteria: General Exclusion Criteria for all Adolescent Cohorts:

• Presence of any contraindication for MRI:

* Cardiac pacemakers
* Metal clips on blood vessels (also called stents)
* Artificial heart valve, artificial arms, hands, legs, etc.
* Brain stimulator devices
* Implanted drug pumps
* Ear or eye implants
* Known metal fragments in eyes
* Exposure to metal filings or shrapnel (sheet metal workers, welders, and others)
* Other metallic surgical hardware in vital area
* Certain tattoos with metallic ink
* Certain intrauterine devices (IUDs) containing metal
* Any other metallic objects that are deemed a contraindication to MRI that cannot be removed
* Certain transdermal (skin) patches such as:

NicoDerm (nicotine for tobacco dependence) Transderm Scop (scopolamine for motion sickness) Ortho Evra (birth control)

* Presence of medical or neurological illness that could impact fMRI measures of cerebral blood flow (e.g., head injury resulting in loss of consciousness greater than 5 minutes, seizure, tic disorder, serious/unstable cardiac, hepatic, renal, respiratory, endocrine, neurologic or hematologic illnesses)
* Clinical/Laboratory Evidence of Hypothyroidism or Hyperthyroidism
* Use of hormonal replacement therapy, anabolic steroids
* Lifetime history of electroconvulsive therapy
* Current tobacco product use
* Lifetime use of any psychotropic medication
* Clinically significant levels of depressive symptoms according to the Children's Depression Rating Scale-Revised (T Score \> 54, Poznanski et al., 1996)
* Diagnosis of a neurodevelopmental disorder (e.g., Autism Spectrum Disorder, Learning Disorder w/ impairment in reading) that would interfere with study tasks (e.g., understanding and completing lengthy battery of questionnaires, ability to complete fMRI scan session and tasks without moving)

Additional Exclusion Criteria for Female Adolescents with a Parental History of MDD, high-risk group:

• Lifetime or current Diagnostic and Statistical Manual (DSM)-5 diagnoses of MDD, persistent depressive disorder, schizophrenia spectrum or other psychotic disorder, bipolar disorder, substance/alcohol use disorder, eating disorders, and posttraumatic stress disorder

Additional Exclusion Criteria for Female Adolescents without a Parental History of MDD, low-risk group:

* Any past or current Diagnostic and Statistical Manual (DSM)-5 psychiatric or substance/alcohol use disorder
* First-degree relative history of any psychiatric disorder

Where this trial is running

Belmont, Massachusetts

• McLean Hospital — Belmont, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Emily Belleau, Ph.D. — Mclean Hospital
• Study coordinator: Emily Belleau

Conditions Major Depressive Disorder; stress; depression; adolescents; neuroimaging; familial risk